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Salmonella flagella confer anti-tumor immunological effect via activating Flagellin/TLR5 signalling within tumor

Jianxiang Chen1,2,3, Yiting Qiao1,4, Guo Chen1

  • 1School of Life Sciences, Nanjing University, Nanjing 210023, China.

Acta Pharmaceutica Sinica. B
|November 3, 2021
PubMed

Insights

Salmonella bacteria can fight cancer by activating the host immune response. This therapy relies on bacterial flagella interacting with Toll-like receptor 5 (TLR5) signaling for anti-tumor effects.

Area of Science:

  • Immunology
  • Microbiology
  • Oncology

Background:

  • Salmonella-mediated cancer therapy shows promise in preclinical models.
  • The precise mechanisms underlying its anti-tumor effects are not fully understood.
  • The host immune response is implicated in Salmonella's therapeutic action.

Purpose of the Study:

  • To elucidate the role of bacterial flagella in Salmonella-mediated cancer therapy.
  • To investigate the involvement of the Flagellin/Toll-like receptor 5 (TLR5) signaling pathway.
  • To assess the therapeutic potential of targeting this pathway for cancer immunotherapy.

Main Methods:

  • Comparison of Salmonella's anti-tumor effects in immunocompetent versus immunodeficient mice.
  • Genetic disruption of flagella in Salmonella strains.
  • Assessment of therapeutic efficacy using melanoma allografts.
  • Exogenous activation of TLR5 signaling using recombinant Flagellin and TLR5 expression.

Main Results:

  • Flagellum-deficient Salmonella strains exhibited significantly reduced anti-tumor effects.
  • The presence of flagella was crucial for inducing the host immune response and tumor suppression.
  • Exogenous activation of TLR5 signaling enhanced the efficacy of flagellum-deficient Salmonella.
  • The Flagellin/TLR5 pathway is a key mediator of Salmonella's anti-cancer activity.

Conclusions:

  • The host immune response, particularly via the Flagellin/TLR5 pathway, is critical for Salmonella-mediated cancer therapy.
  • Flagella are essential components for Salmonella to elicit anti-tumor effects.
  • TLR5 agonists represent a promising strategy for developing novel cancer immunotherapies.
Keywords:
AKT, Akt serine/threonine kinaseBacteria-mediated cancer therapyCFU, colony-forming unitsCTLA-4, cytotoxic T-lymphocyte-associated protein 4Cancer immune therapyDN, dominant-negativeERBB2, Erb-B2 receptor tyrosine kinase 2ERKl, extracellular regulated protein kinase 1FlagellinFlagellumGAPDH, glyceraldehyde-3-phosphate dehydrogenaseGFP, green fluorescent proteinIFN-γ, interferon-γIL, interleukinsIκB, inhibitor of NF-κBJNK, c-Jun N-terminal kinaseLPS, lipopolysaccharideLRR, leucine-rich repeatMyD88, myeloid differentiation factor 88NF-κBNF-κB, nuclear factor kappa-BPBS, phosphate-buffered salinePCR, polymerase chain reactionPD-1, programmed cell death protein-1PD-L1, programmed cell death-ligand 1PEI, polyethylenimineSalmonellaTIR, Toll/Interleukin-1 receptorTLR, Toll-like receptorTLR5TME, tumor microenvironmentTRAF6, TNF receptor associated factor 6VNP20009i.p., intraperitoneallyi.t., intratumorally

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